My question is on assigning the correct 797 risk to a compounded product (e.g., low vs. medium). My NICU Pharmacy compounds low concentration injectables for the neonate patient population. For example, 1ml of drug is placed in a sterile vial and brought up to 10ml with 0.9% saline. Then two dose specific unit of use syringes are drawn up for the patients q12hr doses.
Does 797 consider the above product low or medium risk? I feel it is medium but my other colleagues are not convinced. My ultimate goal is to determine if the syringes need to be made in our clean room or can be compounded in a satellite pharmacy hood. If medium risk I'm aware it has to be in the clean room.
Your BUD talk today was very helpful. It clarified, for my operation, that staying within 797 BUD guidelines is the path I need to take.
Here are five questions from our live presentation, we will continue to post questions from the webinar in such increments.
Q: Is drawing up a solution from a manufacturer vial and into dose syringes considered compounding – and therefore subject to BUD of low risk?
Q: How should we use or interpret information on product stability supplied by manufacturers or compounding firms?
Q: Does a compounded batch need to be sequestered for 14 days while testing is conducted?
Q: We have talked with our microbiologists - they are comfortable with testing the positive controls - but would prefer that we do the sterility testing. Assuming adequate procedures would the QT micro system be an adequate way for us to do membrane filtration testing?
Q: Based on your earlier comments, no MDV should be used beyond 28 days. So no insulin vial should ever be used by a patient for more than 28 days?
My question is regarding beyond use dating in batches of CSP's where the appropriate test for sterility has been performed and the batch has been found after 14 days to be compliant. Does the beyond use date then become the published length of time that the product has been shown to be stable?
08-08-201010:23 PM - last edited on 08-09-201010:59 AM by HeatherQ
jkusmie1 wrote:
Hello Eric,
My question is on assigning the correct 797 risk to a compounded product (e.g., low vs. medium). My NICU Pharmacy compounds low concentration injectables for the neonate patient population. For example, 1ml of drug is placed in a sterile vial and brought up to 10ml with 0.9% saline. Then two dose specific unit of use syringes are drawn up for the patients q12hr doses.
Does 797 consider the above product low or medium risk? I feel it is medium but my other colleagues are not convinced. My ultimate goal is to determine if the syringes need to be made in our clean room or can be compounded in a satellite pharmacy hood. If medium risk I'm aware it has to be in the clean room.
Your BUD talk today was very helpful. It clarified, for my operation, that staying within 797 BUD guidelines is the path I need to take.
John
John,
Thank you. Making dilution bags of injectables is a common practice for neonates and pediatrics. My definition of low-risk prcoedure is a simple but complete aseptic transfer of 1-2 ingredients into a final container. I, too would interpret the risk level of your described procedure to be medium-risk level compounding activities. Using the BUDs in USP 797 is a conservative decision but one that I concur with. The key in making those dates work is by managing the process.
08-08-201011:01 PM - last edited on 08-09-201010:59 AM by HeatherQ
Responses to the questions in Heather's post.
Q: Is drawing up a solution from a manufacturer vial and into dose syringes considered compounding – and therefore subject to BUD of low risk?
A: Yes, according to the definitions in USP Chapter <797>.
Q: How should we use or interpret information on product stability supplied by manufacturers or compounding firms?
A:I don't understand your question. Do you have concerns about the data from compounding firms?
Q: Does a compounded batch need to be sequestered for 14 days while testing is conducted?
A: Ideally, the first few batches should be quarantined until you get a track record of zero sterility failures. If you dispense the CSPs before the 14 day results are available, you need to inspect the media every day (according to the chapter) and have the ability to recall the CSP and identify what patients received the potentially contaminated CSP.
Q: We have talked with our microbiologists - they are comfortable with testing the positive controls - but would prefer that we do the sterility testing. Assuming adequate procedures would the QT micro system be an adequate way for us to do membrane filtration testing?
A: Why don't your microbiologists want to do the sterility tests? It is important that you review the requirements of USP Chapter <71> and compare them against the procedures used with the QT micro system in order to determine process adequancy.
Q: Based on your earlier comments, no MDV should be used beyond 28 days. So no insulin vial should ever be used by a patient for more than 28 days?
A: The chapter says 28 days or otherwise specified by the manufacturer. Sorry if I wasn't clear. Some insulin preparations have dating from the manufacturer for up to 42 days.
08-08-201011:04 PM - last edited on 08-09-201011:00 AM by HeatherQ
Benjamin wrote:
My question is regarding beyond use dating in batches of CSP's where the appropriate test for sterility has been performed and the batch has been found after 14 days to be compliant. Does the beyond use date then become the published length of time that the product has been shown to be stable?
Thank you
Benjamin,
If, after 14 days, your sterility testing results are negative (no growth), then you can extend the dating of that batch to the drug's chemical stability data as published in references.
If your batch passes the sterility test, then you can use chemical stability of the drug as published in Trissel's Handbook of Injectable Drugs or some other similar reference. It is important that the container of the drug maintains it integrity during the storage period because it is integral part of the stability/sterilty system.
Q: Can you comment on ther interplay of closed system transfer devices & BUD?
A: CSTDs have an interesting potential to extend the dating of single-dose vials but to my knowledge, no studies have been published proving that point. Any media fill supply with a CSTD needs to demonstrate zero growth.
Q: Is it recommended to dispense extended BUD CSPs before the final 14 day results if there's a well-established recall procedure?
A: I would not recommend it unless you have good results from previous sterility test results.
Q: How do standards in 797 and 71 apply practically to extemporaneously prepared ophthalmic drops for outpatient use?
A: Eye drops have the requirement of being sterile so, yes the standards of USP 797 and 71 (if BUD is extended) applies. If you are fortifying eye drops then you could consider them low-risk level and give them 14 day refrigerated BUD.
Q: How do you determine BUD for batches that have passed sterility tests? Would you refer to stability data?
A: I would refer to stability data. See my response to an earlier question is this post.
Q: What is the number of intermediate risk CSPs I can batch without needing to do BUD testing?
A: Your question is an oxymoron. Batching and immediate-use do not go together since batching is considered medium-risk level compounding AND not consistent with the elements of compliance for immediate use.
